Activation of RIG-I-like Receptor Signal Transduction

Crit Rev Biochem Mol Biol. Mar-Apr 2012;47(2):194-206. doi: 10.3109/10409238.2011.630974. Epub 2011 Nov 8.

Abstract

Mammalian cells have the ability to recognize virus infection and mount a powerful antiviral response. Pattern recognition receptor proteins detect molecular signatures of virus infection and activate antiviral signaling cascades. The RIG-I-like receptors are cytoplasmic DExD/H box proteins that can specifically recognize virus-derived RNA species as a molecular feature discriminating the pathogen from the host. The RIG-I-like receptor family is composed of three homologous proteins, RIG-I, MDA5, and LGP2. All of these proteins can bind double-stranded RNA species with varying affinities via their conserved DExD/H box RNA helicase domains and C-terminal regulatory domains. The recognition of foreign RNA by the RLRs activates enzymatic functions and initiates signal transduction pathways resulting in the production of antiviral cytokines and the establishment of a broadly effective cellular antiviral state that protects neighboring cells from infection and triggers innate and adaptive immune systems. The propagation of this signal via the interferon antiviral system has been studied extensively, while the precise roles for enzymatic activities of the RNA helicase domain in antiviral responses are only beginning to be elucidated. Here, current models for RLR ligand recognition and signaling are reviewed.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Immunity, Innate / immunology
  • Protein Structure, Tertiary
  • RNA Helicases / chemistry
  • RNA Helicases / genetics
  • RNA Helicases / immunology
  • RNA, Viral / genetics
  • RNA, Viral / immunology
  • Receptors, Pattern Recognition / chemistry
  • Receptors, Pattern Recognition / genetics
  • Receptors, Pattern Recognition / immunology*
  • Signal Transduction*
  • Virus Diseases / immunology

Substances

  • RNA, Viral
  • Receptors, Pattern Recognition
  • RNA Helicases